The proposed work is designed to elucidate the role of the vitreous in the induction of neovascularization in patients with proliferative diabetic retinopathy. We have and are continuing to define the protease inhibitor(s) present in normal human vitreous and comparing these inhibitors to those in diabetic vitreous as far as type of inhibitors as well as spectrum of enzyme inhibited. Furthermore, we are attempting to define whether the vitreous plays a role in vascular endothelial cell proliferation and whether in diabetics there is an increase in angiogenic factors. Because the growth of blood vessels is directional we are also attempting to determine whether the vitreous, normal and diabetic, contains factors which may be chemotactic to endothelial cells. We have now established a reproducible system to assay for chemotaxis of endothelial cells using blindwell chambers.